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https://www.readbyqxmd.com/read/28096417/phosphorylation-by-pkc-and-pka-regulate-the-kinase-activity-and-downstream-signaling-of-wnk4
#1
Maria Castañeda-Bueno, Juan Pablo Arroyo, Junhui Zhang, Jeremy Puthumana, Orlando Yarborough, Shigeru Shibata, Lorena Rojas-Vega, Gerardo Gamba, Jesse Rinehart, Richard P Lifton
With-no-lysine kinase 4 (WNK4) regulates electrolyte homeostasis and blood pressure. WNK4 phosphorylates the kinases SPAK (Ste20-related proline alanine-rich kinase) and OSR1 (oxidative stress responsive kinase), which then phosphorylate and activate the renal Na-Cl cotransporter (NCC). WNK4 levels are regulated by binding to Kelch-like 3, targeting WNK4 for ubiquitylation and degradation. Phosphorylation of Kelch-like 3 by PKC or PKA downstream of AngII or vasopressin signaling, respectively, abrogates binding...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28094285/urinary-exosomes-contain-micrornas-capable-of-paracrine-modulation-of-tubular-transporters-in-kidney
#2
Tannia Gracia, Xiaonan Wang, Ya Su, Elizabeth E Norgett, Timothy L Williams, Pablo Moreno, Gos Micklem, Fiona E Karet Frankl
Exosomes derived from all nephron segments are present in human urine, where their functionality is incompletely understood. Most studies have focused on biomarker discovery rather than exosome function. Through sequencing we identified the miRNA repertoire of urinary exosomes from healthy volunteers; 276 mature miRNAs and 345 pre-miRNAs were identified (43%/7% of reads). Among the most abundant were members of the miR-10, miR-30 and let-7 families. Targets for the identified miRNAs were predicted using five different databases; genes encoding membrane transporters and their regulators were enriched, highlighting the possibility that these miRNAs could modulate key renal tubular functions in a paracrine manner...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28094030/glucocorticoid-induced-leucine-zipper-protein-regulates-sodium-and-potassium-balance-in-the-distal-nephron
#3
Priyanka Rashmi, GianLuca Colussi, Michael Ng, Xinhao Wu, Atif Kidwai, David Pearce
Glucocorticoid induced leucine zipper protein (GILZ) is an aldosterone-regulated protein that controls sodium transport in cultured kidney epithelial cells. Mice lacking GILZ have been reported previously to have electrolyte abnormalities. However, the mechanistic basis has not been explored. Here we provide evidence supporting a role for GILZ in modulating the balance of renal sodium and potassium excretion by regulating the sodium-chloride cotransporter (NCC) activity in the distal nephron. Gilz(-/-) mice have a higher plasma potassium concentration and lower fractional excretion of potassium than wild type mice...
January 13, 2017: Kidney International
https://www.readbyqxmd.com/read/28070462/simulated-mussel-mortality-thresholds-as-a-function-of-mussel-biomass-and-nutrient-loading
#4
Jeremy S Bril, Kathryn Langenfeld, Craig L Just, Scott N Spak, Teresa J Newton
A freshwater "mussel mortality threshold" was explored as a function of porewater ammonium (NH4(+)) concentration, mussel biomass, and total nitrogen (N) utilizing a numerical model calibrated with data from mesocosms with and without mussels. A mortality threshold of 2 mg-N L(-1) porewater NH4(+) was selected based on a study that estimated 100% mortality of juvenile Lampsilis mussels exposed to 1.9 mg-N L(-1) NH4(+) in equilibrium with 0.18 mg-N L(-1) NH3. At the highest simulated mussel biomass (560 g m(-2)) and the lowest simulated influent water "food" concentration (0...
2017: PeerJ
https://www.readbyqxmd.com/read/28004876/towards-the-development-of-small-molecule-mo25-binders-as-potential-indirect-spak-osr1-kinase-inhibitors
#5
Hachemi Kadri, Mubarak A AlAmri, Iva H Navratilova, Luke J Alderwick, Nigel S Simpkins, Youcef Mehellou
The binding of the scaffolding protein MO25 to SPAK and OSR1 protein kinases, which regulate ion homeostasis, causes up to 100-fold increase in their catalytic activity. Since various animal models showed that the inhibition of SPAK and OSR1 lowers blood pressure, we herein present a novel indirect approach for inhibiting SPAK and OSR1 kinases by targeting their protein partner MO25. To explore this approach, we developed fluorescent polarization assay and used it in screening a small in-house library of ca...
December 22, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28003191/calcineurin-inhibitor-cyclosporine-a-activates-renal-na-k-cl-cotransporters-via-local-and-systemic-mechanisms
#6
Katharina Ilse Blankenstein, Aljona Borschewski, Robert Labes, Alexander Paliege, Christin Boldt, James A McCormick, David H Ellison, Michael Bader, Sebastian Bachmann, Kerim Mutig
Calcineurin dephosphorylates NFAT transcription factors, thereby facilitating T-cell mediated immune responses. Calcineurin inhibitors are instrumental for immunosuppression after organ transplantation, but may cause side effects including hypertension and electrolyte disorders. Kidneys were recently shown to display activation of the furosemide-sensitive Na-K-2Cl cotransporter (NKCC2) of the thick ascending limb and the thiazide-sensitive Na-Cl cotransporter (NCC) of the distal convoluted tubule upon calcineurin inhibition using cyclosporin A (CsA)...
December 21, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27986254/inhibition-of-na-k-cl-cotransporter-isoform-1-reduces-lung-injury-induced-by-ischemia-reperfusion
#7
Chou-Chin Lan, Chung-Kan Peng, Shih-En Tang, Hsueh-Ju Lin, Sung-Sen Yang, Chin-Pyng Wu, Kun-Lun Huang
OBJECTIVES: Ischemia-reperfusion acute lung injury is characterized by increased vascular permeability, lung edema, and neutrophil sequestration. Ischemia-reperfusion acute lung injury occurs in lung transplantation and other major surgical procedures. Effective regulation of alveolar fluid balance is critical for pulmonary edema. Sodium-potassium-chloride co-transporter regulates alveolar fluid and is associated with inflammation. We hypothesized that sodium-potassium-chloride co-transporter is important in ischemia-reperfusion acute lung injury...
January 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/27983989/potassium-depletion-stimulates-na-cl-cotransporter-via-phosphorylation-and-inactivation-of-the-ubiquitin-ligase-kelch-like-3
#8
Kenichi Ishizawa, Ning Xu, Johannes Loffing, Richard P Lifton, Toshiro Fujita, Shunya Uchida, Shigeru Shibata
Kelch-like 3 (KLHL3) is a component of an E3 ubiquitin ligase complex that regulates blood pressure by targeting With-No-Lysine (WNK) kinases for degradation. Mutations in KLHL3 cause constitutively increased renal salt reabsorption and impaired K(+) secretion, resulting in hypertension and hyperkalemia. Although clinical studies have shown that dietary K(+) intake affects blood pressure, the mechanisms have been obscure. In this study, we demonstrate that the KLHL3 ubiquitin ligase complex is involved in the low-K(+)-mediated activation of Na-Cl cotransporter (NCC) in the kidney...
October 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27942049/potassium-depletion-stimulates-na-cl-cotransporter-via-phosphorylation-and-inactivation-of-the-ubiquitin-ligase-kelch-like-3
#9
Kenichi Ishizawa, Ning Xu, Johannes Loffing, Richard P Lifton, Toshiro Fujita, Shunya Uchida, Shigeru Shibata
Kelch-like 3 (KLHL3) is a component of an E3 ubiquitin ligase complex that regulates blood pressure by targeting With-No-Lysine (WNK) kinases for degradation. Mutations in KLHL3 cause constitutively increased renal salt reabsorption and impaired K(+) secretion, resulting in hypertension and hyperkalemia. Although clinical studies have shown that dietary K(+) intake affects blood pressure, the mechanisms have been obscure. In this study, we demonstrate that the KLHL3 ubiquitin ligase complex is involved in the low-K(+)-mediated activation of Na-Cl cotransporter (NCC) in the kidney...
2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27905692/remote-pre-procedural-ischemic-stroke-was-the-strongest-risk-for-stroke-and-death-associated-with-carotid-stenting-a-single-center-experience
#10
Mária Rašiová, Ľubomír Špak, Ľudmila Farkašová, Štefan Pataky, Martin Koščo, Marek Hudák, Matej Moščovič, Norbert Leško
BACKGROUND: The goal of carotid artery stenting (CAS) is to decrease the stroke risk in patients with carotid stenosis. This procedure carries an immediate risk of stroke and death and many patients do not benefit from it, especially asymptomatic patients. Patient selection for carotid procedure who benefit from procedure and who is the procedure hazardous for is important. Remote ischemic stroke is known risk factor for stroke reccurence during surgery. The aim of our study was to determine the periprocedural complication risk (within 30 days after CAS) associated with carotid stenting (stroke, death) between patients with remote pre- procedural ischemic stroke and without it; to analyse periprocedural risk in other specific patient subgroups treated with CAS and to determine the impact of observed variables on all- cause mortality during long-term follow-up...
December 1, 2016: International Angiology: a Journal of the International Union of Angiology
https://www.readbyqxmd.com/read/27853306/osr1-and-spak-cooperatively-modulate-sertoli-cell-support-of-mouse-spermatogenesis
#11
Yung-Liang Liu, Sung-Sen Yang, Shyi-Jou Chen, Yu-Chun Lin, Chin-Chen Chu, Hsin-Hui Huang, Fung-Wei Chang, Mu-Hsien Yu, Shih-Hua Lin, Gwo-Jang Wu, Huey-Kang Sytwu
We investigated the role of oxidative stress-responsive kinase-1 (OSR1) and STE20 (sterile 20)/SPS1-related proline/alanine-rich kinase (SPAK), upstream regulators of the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1)-essential for spermatogenesis-in mouse models of male fertility. Global OSR1(+/-) gene mutations, but not global SPAK(-/-) or Sertoli cell (SC)-specific OSR1 gene knockout (SC-OSR1(-/-)), cause subfertility with impaired sperm function and are associated with reduced abundance of phosphorylated (p)-NKCC1 but increased p-SPAK expression in testicular tissue and spermatozoa...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27782176/functional-kinomics-establishes-a-critical-node-of-volume-sensitive-cation-cl-cotransporter-regulation-in-the-mammalian-brain
#12
Jinwei Zhang, Geng Gao, Gulnaz Begum, Jinhua Wang, Arjun R Khanna, Boris E Shmukler, Gerrit M Daubner, Paola de Los Heros, Paul Davies, Joby Varghese, Mohammad Iqbal H Bhuiyan, Jinjing Duan, Jin Zhang, Daniel Duran, Seth L Alper, Dandan Sun, Stephen J Elledge, Dario R Alessi, Kristopher T Kahle
Cell volume homeostasis requires the dynamically regulated transport of ions across the plasmalemma. While the ensemble of ion transport proteins involved in cell volume regulation is well established, the molecular coordinators of their activities remain poorly characterized. We utilized a functional kinomics approach including a kinome-wide siRNA-phosphoproteomic screen, a high-content kinase inhibitor screen, and a kinase trapping-Orbitrap mass spectroscopy screen to systematically identify essential kinase regulators of KCC3 Thr(991)/Thr(1048) phosphorylation - a key signaling event in cell swelling-induced regulatory volume decrease (RVD)...
October 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27771793/identification-and-characterization-of-a-new-member-of-the-genus-luteovirus-from-cherry
#13
O Lenz, J Přibylová, J Fránová, I Koloniuk, J Špak
The complete genomic sequence of a new virus from cherry trees was determined. Its genome is 5857 nt long and resembles that of members of the genus Luteovirus in its genomic organization and nucleotide sequence. Based on the species demarcation criteria for luteoviruses, the virus represents a new luteovirus species. Furthermore, a 47-nt-long inverted repeat was found at the 3' end of its genome. The virus has been provisionally named cherry-associated luteovirus (ChALV) and is the fourth member of the family Luteoviridae reported to naturally infect woody plants...
October 22, 2016: Archives of Virology
https://www.readbyqxmd.com/read/27754152/os-29-04-sympathetic-nervous-system-regulation-of-the-renal-ncc-and-blood-pressure-during-high-dietary-salt-intake
#14
Richard Wainford, Kathryn Walsh
OBJECTIVE: These studies tested the hypothesis that the SNS release of norepinephrine modulates NCC activity via a WNK1 mechanism to contribute to the pathophysiology of salt-sensitive hypertension in rats. DESIGN AND METHOD: Male Sprague-Dawley (SD) rats receiving a continuous s.c. saline or NE (600 ng/min) infusion or naïve Dahl Salt-Resistant (DSR) and Dahl Salt-Sensitive (DSS) rats were fed a 0.6% (NS) or 8% NaCl (HS) diet for 14 or 21 days respectively (N = 6/group)...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27753931/os-05-06-in-primary-aldosteronism-mineralocorticoids-and-potassium-influence-abundance-of-the-thiazide-sensitive-sodium-chloride-cotransporter
#15
Wolley Mj, Wu A, Xu S, Gordon Rd, Fenton Ra, Stowasser M
BACKGROUND: Distal tubular sodium retention is a potent driver of hypertension, with the thiazide sensitive sodium-chloride cotransporter (NCC) a key player. The upstream modulators of NCC are unclear, but recent evidence has revealed the kinases 'with-no-lysine kinase 4' (WNK4) and 'STE20/SPS1-related, proline alanine-rich kinase' (SPAK) to be involved. The wider role of mineralocorticoids is poorly understood, but animal models implicate aldosterone as a potent regulator, possibly via effects on plasma potassium...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27720946/6-3-4-dihydro-1h-isoquinoline-2-yl-n-6-methoxypyridine-2-yl-nicotinamide-26-dimn-26-decreases-cell-proliferation-by-induction-of-apoptosis-and-downregulation-of-androgen-receptor-signaling-in-human-prostate-cancer-cells
#16
Hye-Eun Choi, Ji-Sun Shin, Dong-Gyu Leem, Soo-Dong Kim, Won-Jea Cho, Kyung-Tae Lee
Previously, we reported that 6-(3,4-dihydro-1H-isoquinolin-2-yl)-N-(6-methylpyridin-2-yl) nicotinamide (DIMN) analogues inhibited the growth of prostate cancer cells as an anti-androgenic compound. In the present study, we evaluated cytotoxic effects of these DIMN derivatives and found that DIMN-26 most potently inhibited the proliferation of the LNCap-LN3 androgen-dependent and DU145 androgen-independent prostate cancer cells through induction of G2/M phase cell cycle arrest and subsequent apoptosis. The G2/M phase arrest was found due to increases in the activation of cdc2 (also known as cyclin-dependent kinase 1, CDK1)/cyclin B1 complex...
December 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27701672/sv%C3%A3-rt-att-s%C3%A3-ka-och-f%C3%A3-hj%C3%A3-lp-f%C3%A3-r-alkoholproblem-yrkesverksamma-socialt-etablerade-f%C3%A3-redrar-individuell-samtalsbehandling-och-privat-v%C3%A3-rdgivare-visar-enk%C3%A3-tstudie
#17
Solveig Hausken, Rickard Lönner, Claudia Fahlke, Fredrik Spak
Survey of early alcohol  treatment preferences shows higher confidence in face to face meetings Adult men and women (n = 307), working and living in the area of south west Sweden, answered a web based questionnaire where they graded treatment and caregiver preferences while imagining themselves developing an alcohol problem. Alcohol consumption was measured using AUDIT-C. Face-to-face delivered treatment was preferred over telephone or internet based advice. About 53 percent of the men and women considered treatment given by primary health as poor...
October 4, 2016: Läkartidningen
https://www.readbyqxmd.com/read/27643324/os-05-06-in-primary-aldosteronism-mineralocorticoids-and-potassium-influence-abundance-of-the-thiazide-sensitive-sodium-chloride-cotransporter
#18
Wolley Mj, Wu A, Xu S, Gordon Rd, Fenton Ra, Stowasser M
BACKGROUND: Distal tubular sodium retention is a potent driver of hypertension, with the thiazide sensitive sodium-chloride cotransporter (NCC) a key player. The upstream modulators of NCC are unclear, but recent evidence has revealed the kinases 'with-no-lysine kinase 4' (WNK4) and 'STE20/SPS1-related, proline alanine-rich kinase' (SPAK) to be involved. The wider role of mineralocorticoids is poorly understood, but animal models implicate aldosterone as a potent regulator, possibly via effects on plasma potassium...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27643082/os-29-04-sympathetic-nervous-system-regulation-of-the-renal-ncc-and-blood-pressure-during-high-dietary-salt-intake
#19
Richard Wainford, Kathryn Walsh
OBJECTIVE: These studies tested the hypothesis that the SNS release of norepinephrine modulates NCC activity via a WNK1 mechanism to contribute to the pathophysiology of salt-sensitive hypertension in rats. DESIGN AND METHOD: Male Sprague-Dawley (SD) rats receiving a continuous s.c. saline or NE (600 ng/min) infusion or naïve Dahl Salt-Resistant (DSR) and Dahl Salt-Sensitive (DSS) rats were fed a 0.6% (NS) or 8% NaCl (HS) diet for 14 or 21 days respectively (N = 6/group)...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27601609/unique-characteristics-of-cryptococcosis-identified-after-death-in-patients-with-liver-cirrhosis-comparison-with-concurrent-cohort-diagnosed-antemortem
#20
Nina Singh, Costi D Sifri, Fernanda P Silveira, Rachel Miller, Kevin S Gregg, Shirish Huprikar, Erika D Lease, Andrea Zimmer, J Stephen Dummer, Cedric W Spak, Christine Koval, David B Banach, Miloni Shroff, Jade Le, Darin Ostrander, Robin Avery, Albert Eid, Raymund R Razonable, Jose Montero, Emily Blumberg, Ahlaam Alynbiawi, Michele I Morris, Henry B Randall, George Alangaden, Jeffrey Tessier, Thomas V Cacciarelli, Marilyn M Wagener, Hsin Yun Sun
Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully known. In a multicenter study, data generated as standard of care was systematically collected in 113 consecutive patients with cirrhosis and cryptococcosis followed for 80 patient-years. The diagnosis of cryptococcosis was first established after death in 15.9% (18/113) of the patients. Compared to cases diagnosed while alive, these patients had higher MELD score (33 vs. 22, P = .029) and higher rate of cryptococcemia (75...
September 6, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
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